On a clinical and theoretical background some fundamental symptoms of schizophrenia incl. affective flattening, avolition, asociality and thought disorders are considered to relate to persistent neurobiological changes involving the prefrontal and temporal cortex. The fronto- striato-thalamo-cortical loops are secondarily involved. This theory defines hypothesis concerning aberration of regions of interest ie prefrontal cortex, striatum, thalamus and temporal lobe. The specific aims are; 1. To relate psychopathology in clinical subgroups of newly diagnosed psychoses with neurobiological findings and 2. To measure clinical group stability and possible neurobiological abnormalities during the course of disease. The study comprises a prospective cohort including all cases aged 19-45 gamma of first episode (non-organic) psychoses in the City of Copenhagen. A total of 80 patients including 50 cases of schizophrenia or schizophreniform disorder and 24 normal healthy volunteers have been included. The initial findings from two consequtive groups of patients and controls are in support of an aberrant prefronto-striatal functional interrelationship and also suggest that the structural lesions are mainly cortical in newly diagnosed schizophrenics. The above mentioned fundamental symptoms correlated with higher prefrontal RCBF during cognitive activation although all patient groups were subnormal. Hallucinations and delusions correlated with inability to suppress striatal activity. Semantic aspects of memory were selectively impaired in the patients. A further 16-cases are included in order to define initial effects of neuroleptic treatment. The application concerns reinvestigation of the whole cohort of 80+16 cases and 24 controls 3-4 years after the initial study. The repeated investigational programme includes psychopathology (incl. SCAN), prodromal signs, perinatal events, RCBF (cognition and control task), CT- scan, MRI (at reinvestigation) and neuropsychology. The study is significant 1. Because cortico-subcortical function has never been investigated during mental activation in recently diagnosed cases also investigated by CT-MRI. 2. A long term follow-up documenting exactly the same variables in the same cases during the course of disease has never been performed. This enables a delineation of clinical subgroups according to biological aberrations (trait and state markes) and a mapping of biological course of aberrations in clinically defined subgroups as well as possible biological outcome predictors at first investigation. Relocation oc cases for follow-up is facilitated by the nation-wide psychiatric admission case register in Denmark.